Dopamine D1-like receptors agonist SKF 38393 increases cFOS expression in the paraventricular nucleus of the hypothalamus--impact of acute and chronic cocaine.
The present study indicates that activation of dopamine D1-like receptors by administration of SKF 38393 leads to dose-dependent (doses: 5, 10 and 20 mg/kg) increases in the expression of cFos proteins in the rat paraventricular nucleus of the hypothalamus (PVN). This effect was abolished by administration of SCH 23390, a dopamine D1-like receptor antagonist (0.5 and 1 mg/kg, given 30 min before SKF 38393--10 mg/kg), suggesting that the apparent effect is specific for activation of dopamine D1-like receptors. Expression of cFos after SKF 38393 (10 mg/kg) was observed in some, but not all, CRF-immunoreactive neurons, as well as in small portion of oxytocin- but not vasopressin-immunoreactive neurons (double-immunofluorescence experiments). There were also certain populations of nuclei that showed expression of cFos but did not co-localize with the above markers. We also found that both acute and repeated (once daily for 5 consecutive days) exposure to cocaine (25 mg/kg) attenuated the induction of cFos expression triggered by SKF 38393 when administered 24 hours after single or the last dose of cocaine (25 mg/kg). Attenuation was observed at the same level after single and chronic exposure to cocaine, indicating a rapid functional down-regulation of dopamine D1-like receptors that are resistant to subsequent doses of cocaine. These data provide evidence for the functional role of dopamine D1-like receptors in the PVN and indicate a functional adaptation of dopamine D1-like receptors following a single dose of cocaine without further progression of adaptation or resistance of D1-like receptor-mediated genomic function in the course of repeated cocaine intake.
Chocyk
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Laboratory of Pharmacology and Brain Biostructure, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. chocyk@if-pan.krakow.pl
Czyrak
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Wedzony
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D010121:Oxytocin / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D009435:Synaptic Transmission / Q000187:drug effects; D014667:Vasopressins / Q000502:physiology
D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D014667:Vasopressins; D010121:Oxytocin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine